PMID- 11798838
OWN - NLM
STAT- MEDLINE
DCOM- 20020430
LR  - 20121115
IS  - 0376-2491 (Print)
IS  - 0376-2491 (Linking)
VI  - 80
IP  - 9
DP  - 2000 Sep
TI  - [The toxic effects of high-dose Bcl-2 antisense phosphorothioate 
      oligodeoxynucleotides incubation on cell line].
PG  - 694-7
AB  - OBJECTIVE: To investigate the toxic effects of high-dose Bcl-2 antisense 
      phosphorothioate oligodeoxynucleotides (AS-PS-ODN, ASPO) incubation on HL60 cells 
      and to understand the relationship between the dose of ASPO and the toxicity. 
      METHODS: Cellular viability and toxicity were detected by trypan blue exclusion, 
      colony-forming unit HL60 cells and MTT assay. The expression of Bcl-2 protein was 
      determined by immunocytochemistry and flow cytometry analysis. The proportion of 
      apoptosis cells was tested by acridine orange (AO) standing. The sense (PS-ODN, 
      SPO) was chosen for the toxic control of independent sequence. The curves of 
      dose-effect and dose-toxicity were transfered into straight line and the 
      reguession analysis was done by computer with the SPSS soften-ware. RESULTS: When 
      the dose of Bcl-2 PS-ODN was higher than 20 micromol/L, the non-specific effect 
      of suppressing cell proliferation could occur. When the dose of Bcl-2 PS-ODN was 
      more than 160 micromol/L, the non-specific effect (toxic effect) increased 
      significantly. When the dose of Bcl-2 ASPO was higher than 80 micromol/L, the 
      specific effect of inhibitting the expression of Bcl-2 proteion increased slowly. 
      When the dose of PS-ODN reached 262 micromol/L, the toxic effect had no 
      significant differences between Bcl-2 ASPO and Bcl-2 SPO. In the presence of ASPO 
      or SPO at 160 micromol/L, the expression of Bcl-2 protein in the two groups of 
      HL60 was decreased to 28% and 78% respectively, after 72 hours of incubation. The 
      expression of Bcl-2 protein in the groups of HL60 which were passaged after 
      incubation with ASPO or SPO was reinereased to 99.6% and 97.8%, respectively. 
      CONCLUSION: Although ASPO is a kind of low-toxic drug, the toxic effects of Bcl-2 
      ASPO seem to be dependent on the dose increasing to a certain extent. It is clear 
      that it can be used over a wide range of doses, however. Our results may also 
      provide some referring concentrations of Bcl-2 ASPO for the pharmacodynamic and 
      toxicological study in vivo in future.
FAU - Lin, Y
AU  - Lin Y
AD  - Union Hospital Affiliate to Fujian Medical University, Fujian Insititute of 
      Hematology, Fuzhou 350001, China.
FAU - Lu, L
AU  - Lu L
FAU - Chen, Z
AU  - Chen Z
LA  - chi
PT  - English Abstract
PT  - Journal Article
PL  - China
TA  - Zhonghua Yi Xue Za Zhi
JT  - Zhonghua yi xue za zhi
JID - 7511141
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Phosphates)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Thionucleotides)
RN  - 8056RR93HU (phosphorodithioic acid)
SB  - IM
MH  - *Apoptosis
MH  - Cell Survival/drug effects
MH  - Dose-Response Relationship, Drug
MH  - HL-60 Cells
MH  - Humans
MH  - Oligonucleotides, Antisense/chemistry/*toxicity
MH  - Phosphates/chemistry
MH  - Proto-Oncogene Proteins c-bcl-2/*antagonists & inhibitors/biosynthesis
MH  - Thionucleotides/chemistry/*toxicity
MH  - Tumor Cells, Cultured
EDAT- 2002/01/19 10:00
MHDA- 2002/05/01 10:01
CRDT- 2002/01/19 10:00
PHST- 2002/01/19 10:00 [pubmed]
PHST- 2002/05/01 10:01 [medline]
PHST- 2002/01/19 10:00 [entrez]
PST - ppublish
SO  - Zhonghua Yi Xue Za Zhi. 2000 Sep;80(9):694-7.